The present invention relates to a process for preparing known fungicidally active alkylanilides from 2-alkylhaloaromatics and heterocyclylamides.
EP-A-0 824 099 and WO-A-03010149 disclose that alkylanilides are obtained by reacting the appropriate acid chloride with the appropriate alkylaniline derivative.
Both preparation and handling of the acid chlorides and the preparation of the alkylanilides are associated with a considerable level of technical complexity. For example, the acid chlorides have to be purified before the reaction by a time-consuming and costly distillation step.
The anilines are prepared typically, as described in WO-A-3074491, by a complicated synthesis from the corresponding bromoaromatics and benzophenone imine or at temperatures of 150° C. and pressures of from 75 to 85 bar with ammonia gas, as described in WO-A-06061226.
Alkylanilines, however, frequently exhibit toxic properties and are potentially mutagenic.
The prior art discloses that aryl halides can be reacted with amides under palladium or copper catalysis to give alkylanilides (J. Am. Chem. Soc. 2002, 124, 7420).
It is frequently found, however, that metal-catalyzed reactions with heterocycles which can function as chelating ligands are inhibited. Furthermore, ortho-substituted haloaromatics are sterically hindered for a halogen exchange.